Devices for aerosolization (“dry nebulization”) of aerosolizable (“nebulizable”) dry material are known to the skilled person. For example, for the aerosolization of powdery pharmaceutical preparations, so-called dry powder inhalers (DPIs) have been described. In these devices, an aerosolizable material, for example a powdery medical substance, is acted upon by a compressed gas or carrier gas in a specially provided chamber and, within this chamber, is converted to a state which is referred to as aerosol or dry mist. The particles of the material are in this case present in a preferably uniform and finely dispersed form across the entire volume of compressed gas or carrier gas and are then discharged from the chamber in this state via suitable devices.
Such devices can be used for administration of medical substances to spontaneously breathing or ventilated patients. For use in spontaneously breathing patients, the devices are generally connected to a suitable mouthpiece or a breathing mask. In invasive use, i.e. on ventilated patients, these devices feed the aerosolized medical substance into a ventilator system which then delivers the aerosolized material to the patient's lung.
In the devices known hitherto for aerosolization of powdery material, however, the problem generally found was that large amounts of medical substances could be delivered to the patient only, if at all, with considerable outlay in terms of equipment, for example using extensive mechanical dosing devices. Generally, the known devices were suitable for the aerosolization of pharmaceutical quantities in the range from approximately 1 μg up to approximately 20 mg. However, certain medical substances such as, e.g., lung surfactant preparations, require administration of large amounts, for example more than 100 mg or even in the gram range which, when using conventional DPIs, requires very long inhalation times. A second problem of devices known from the art can be the reproducibility of the amount of aerosolized material delivered to the patient. This is particularly the case when during storage or even during action of the inhaler the particles of the aerosolizable material agglomerate to larger particles with a different aerodynamic behaviour. Large particles will have a much smaller chance to reach their target, the deeper lung, since they tend to be deposited in the upper airways or throat or even somewhere in the inhaling apparatus.
The problem of administering large amounts of aerosolizable material such as lung surfactant preparations in precise doses concerns all sections of the apparatus used for inhalation: the air supply and its controller, the aerosolizing unit itself, the piping and valve system (including, where appropriate, the inner surfaces of a ventilator system), and the respiratory endpieces (mask, tube), in other words all sections in which an uncontrolled loss by unwanted deposition of aerosolized particles and thus reduction of the dose delivered to the patient and obstruction may occur.
In conventional aerosolizing units, one problem generally found was that the aerosolizable material, which is present as a loose charge in a storage container, for example a commercially available pharmaceutical vial, tends to agglomerate, by reason of its surface quality and/or its moisture content, which can result in blockage of a comparatively narrow aperture cross section of the vial. Such agglomeration may also occur in lung surfactant preparations. Such blockages can normally be obviated only by suitable mechanical means, in order to ensure a continuous dosing of the aerosolizable material over quite a long period of time. In addition, as already pointed out above, agglomerated particles of aerosolizable material, for example lung surfactant preparations, are not generally able to access the lungs with the same efficiency and following the same local distribution/deposition pattern as smaller, non-agglomerated particles.
In the prior art aerosolizing unit of GB 24 848 A, a reservoir of aerosolizable material is connected via a narrow passage to a chamber into which supply air is pressed by means of a syringe. Deagglomeration of the aerosolized particles takes place as the supplied air is further forced into the reservoir and performs a whirling action therein; where after the dispersed aerosolizable material is expelled through the chamber and out of a nozzle towards the patient. In FR 2 598 918 A the aerosolizable material is, in contrast, conveyed by an Archimedean screw into a jet of compressed air where dispersion takes place.
In many instances it is necessary to ensure rapid and high-dose administration of aerosolizable material, in a form accessible to the alveoli, into the lungs with a constant dosage, in rapid sequence and over a period of several minutes. Both above-mentioned systems cannot, however, provide administration of high doses of aerosolizable material and are, due to their geometry and dispersion mechanism, still prone to agglomeration, e.g. in the chamber or in the hopper provided with the screw, so that accurate dosing remains an issue. In fact, such administration was possible, if at all, only with considerable outlay in terms of equipment.
WO 2006/108558 A1 discloses a device for dosing and powder aerosolization in which deagglomeration of the aerosolizable material, such as a powdery lung surfactant preparation, is achieved by means of pressure compensation between the pressure pulses sent into the aerosolization channel of the device. The shear force necessary for deagglomeration is created by taking advantage of the high pressure during the pulses. While this system delivers superior results over the known prior art systems in terms of concentration of aerosolized material delivered, issues of concern remain regarding residues of aerosolizable material adhering to the inner surfaces of the system such as the reservoir walls or the bottom of the aerosolization channel.
A further issue concerns the output characteristics of a dosing device such as the one disclosed in WO 2006/108558 A1. As the dosing device uses pressure pulses to deagglomerate, the question arises about the effect these may have on the patient. The pressure pulses are of substantial magnitude and, thus, the dosing device cannot be connected directly to the patient's breathing front ends such as masks in the case of spontaneously breathing patients. For ventilated patients, the output of the dosing device must be connected to the ventilator in order to allow for both adequate and precise dosage, and for the necessary oxygen supply. In the case of infants, moreover, the volume and dosage of the supplied aerosol as well as the partial pressure of oxygen as well as the airway pressure are even more critical than in adults and need special consideration. Since for infants the conventional approach of supplying airborne drugs via pressure respirators and tubes is extremely stressful, specialized equipment and rooms are required.